Levy M, Liszauer A, Wexler M J
Can J Physiol Pharmacol. 1983 Nov;61(11):1396-408. doi: 10.1139/y83-200.
The purpose of this study was to determine if the renal circulation of normal and cirrhotic dogs behave similarly in response to an acute endotoxin infusion. Endotoxin was administered as a slow continuous infusion (13-26 micrograms/min) to a total of 20 normal dogs through the femoral vein, portal vein, or into the left renal artery. In each case, there was an initial increment in renal blood flow, of the order of 46%, while arterial blood pressure was actually declining. After 8-20 min, blood flow fell as perfusion pressure declined further. The initial increment in renal perfusion was not due to a hyperthermic response following the endotoxin. When similar doses were given to five dogs with chronic biliary cirrhosis and ascites, the biphasic response in renal perfusion was not observed, rather blood flow declined as perfusion pressure declined. When normal dogs were infused with bilirubin, bile salts, noradrenaline, and angiotensin in pressor doses, the subsequent infusion of endotoxin still produced the usual biphasic response in renal perfusion. Chronic elevation of portal pressure (but not acute elevation), volume contraction by diuresis or hemorrhage, and the infusion of bile intravenously, all abolished the biphasic response in renal perfusion and reproduced in normal dogs the response to endotoxin observed in cirrhotic dogs. Investigation of the factors causing the initial decrease in intrarenal vascular resistance in normal dogs following the endotoxin infusion implicated a role for histamine, kinins, and prostaglandins. We conclude there is a fundamental difference in the response of the renal circulation of normal and cirrhotic dogs to an endotoxin infusion, which may depend on failure of this latter group to release one or more humoral agents. This difference may be due to elevated portal pressure, a decreased effective arterial blood volume, or the products of bile having access to the circulation in cirrhotic dogs.
本研究的目的是确定正常犬和肝硬化犬的肾循环在急性内毒素输注时的反应是否相似。通过股静脉、门静脉或左肾动脉，以缓慢持续输注（13 - 26微克/分钟）的方式给总共20只正常犬输注内毒素。在每种情况下，肾血流量最初都会增加，幅度约为46%，而动脉血压实际上却在下降。8 - 20分钟后，随着灌注压进一步下降，血流量也随之降低。肾灌注的最初增加并非由于内毒素后的体温升高反应。给五只患有慢性胆汁性肝硬化和腹水的犬给予相似剂量时，未观察到肾灌注的双相反应，而是随着灌注压下降血流量也下降。当给正常犬输注胆红素、胆盐、去甲肾上腺素和升压剂量的血管紧张素时，随后输注内毒素仍会在肾灌注中产生通常的双相反应。门静脉压力的慢性升高（而非急性升高）、利尿或出血导致的容量收缩以及静脉内输注胆汁，都会消除肾灌注的双相反应，并使正常犬再现肝硬化犬对内毒素的反应。对内毒素输注后正常犬肾内血管阻力最初降低的相关因素进行研究表明，组胺、激肽和前列腺素起了作用。我们得出结论，正常犬和肝硬化犬的肾循环对内毒素输注的反应存在根本差异，这可能取决于后一组犬无法释放一种或多种体液因子。这种差异可能是由于门静脉压力升高、有效动脉血容量减少或胆汁产物在肝硬化犬中进入循环所致。
